Feasibility of low-cost accelerometers in measuring functional recovery after major oncologic surgery.

BACKGROUND AND OBJECTIVES: Low-cost consumer-based activity monitors (CAMs), such as the Fitbit, are popular for fitness and wellness tracking. Functional status is an excellent predictor of postoperative outcomes, yet objective measurements are resource-intensive. The aim of this study is to demonstrate the feasibility of using activity monitors during the perioperative period in patients undergoing major oncologic surgery. METHODS: An institution review board proved that a prospective study was conducted. CAMs were worn throughout the perioperative period and accelerometer data were collected. Baseline and 21-days follow-up functional measures included short physical performance battery, Community Health Activities Model Program questionnaire, mobility assessment tool-short form, and 400 m walk. RESULTS: A total of 19 of 22 (86%) patients who wore a CAM during the perioperative period had analyzable data. Compliance with wearing the device varied significantly: 100% preadmission, 19% in-hospital, and 82% postdischarge. Median daily steps decreased from preadmission to postdischarge (77% median reduction). Established resource-intensive measures of functional status did not perform well as measures of decreased functional status and activity when comparing baseline to 21-day postdischarge assessments. CONCLUSIONS: Activity monitors are a feasible, low-cost measure of perioperative activity for patients undergoing major surgery, and may be useful in identifying patients vulnerable to postsurgical complications.

Exploration of a F(ab')2 Fragment as the Targeting Agent of α-Radiation Therapy: A Comparison of the Therapeutic Benefit of Intraperitoneal and Intravenous Administered Radioimmunotherapy.

Refinement of treatment regimens enlisting targeted α-radiation therapy (TAT) is an ongoing effort. Among the variables to consider are the target molecule, radionuclide, dosage, and administration route. The panitumumab F(ab')2 fragment targeting epidermal growth factor receptor tolerated modification with the TCMC chelate as well as radiolabeling with 203Pb or 212Pb. Good specific activity was attained when the immunoconjugate was labeled with 212Pb (9.6 ± 1.4 mCi/mg). Targeting of LS-174T tumor xenografts with the 203Pb-panitumumab F(ab')2 demonstrated comparable amounts of uptake to the similarly radiolabeled panitumumab IgG. A dose escalation study was performed to determine an effective working dose for both intraperitoneal (i.p.) and intravenous (i.v.) injections of 212Pb-panitumumab F(ab')2. Therapeutic efficacy, with modest toxicity, was observed with 30 µCi given i.p. Results for the i.v. administration were not as definitive and the experiment was repeated with a higher dose range. From this study, 20 µCi given i.v. was selected as the effective working dose. A subsequent therapy study combined gemcitabine or paclitaxel with i.v. 212Pb-panitumumab F(ab')2, which increased the median survival (MS) of LS-174T tumor-bearing mice to 208 and 239 d, respectively. Meanwhile, the MS of mice treated with i.v. 212Pb-panitumumab F(ab')2 alone was 61 and 11 d for the untreated group of mice. In conclusion, the panitumumab F(ab')2 fragment whether given by i.p. or i.v. injection, is a viable candidate as a delivery vector for TAT of disseminated i.p. disease.

Comparative studies on the therapeutic benefit of targeted α-particle radiation therapy for the treatment of disseminated intraperitoneal disease.

Identification of the appropriate combination of radionuclide, target and targeting vehicle is critical for successful radioimmunotherapy. For the treatment of disseminated peritoneal diseases such as pancreatic or ovarian cancer, α-emitting radionuclides have been proposed for targeted radiation therapy. This laboratory has taken a systematic approach investigating targeted α-radiation therapy, allowing comparisons to now be made between 211At, 227Th, 213Bi and 212Pb. Herein, trastuzumab radiolabeled with 211At and 227Th was evaluated for therapeutic efficacy in the LS-174T i.p. tumor model. A dose escalation study was conducted with each radioimmunoconjugate (RIC). Therapeutic benefit was realized with 211At-trastuzumab with doses of 20, 30 and 40 µCi. At doses >40 µCi, toxicity was observed with greater weight loss and 2-fold higher decrease in the platelet counts. Following a second study comparing the effect of 20, 30 and 40 µCi of 211At-trastuzumab, 30 µCi was selected as the dose for future studies. A parallel study was performed evaluating 0.25, 0.5, 1.0, 2.0 and 5.0 µCi of 227Th-trastuzumab. The 0.5 and 1.0 µCi injected dose resulted in a therapeutic response; a lower degree of weight loss was experienced by the mice in the 0.5 µCi cohort. When the data is normalized for comparing 211At, 227Th, 213Bi and 212Pb, the choice of radionuclide for RIT is perhaps not entirely based on simple therapeutic efficacy, other factors may play a role in choosing the "right" radionuclide.

Targeted α-Particle Radiation Therapy of HER1-Positive Disseminated Intraperitoneal Disease: An Investigation of the Human Anti-EGFR Monoclonal Antibody, Panitumumab.

Identifying molecular targets and an appropriate targeting vehicle, i.e., monoclonal antibodies (mAb) and their various forms, for radioimmunotherapy (RIT) remains an active area of research. Panitumumab, a fully human and less immunogenic mAb that binds to the epidermal growth factor receptor (Erb1; HER1), was evaluated for targeted α-particle radiation therapy using 212Pb, an in vivo α generator. A single dose of 212Pb-panitumumab administered to athymic mice bearing LS-174T intraperitoneal (i.p.) tumor xenografts was found to have greater therapeutic efficacy when directly compared with 212Pb-trastuzumab, which binds to HER2. A dose escalation study determined a maximum effective working dose of 212Pb-panitumumab to be 20µCi with a median survival of 35 days versus 25 days for the untreated controls. Pretreatment of tumor-bearing mice with paclitaxel and gemcitabine 24hours prior to injection of 212Pb-pantiumumab at 10 or 20µCi resulted in the greatest enhanced therapeutic response at the higher dose with median survivals of 106 versus 192 days, respectively. The greatest therapeutic impact, however, was observed in the animals that were treated with topotecan 24hours prior to RIT and then again 24hours after RIT; the best response from this combination was also obtained with the lower 10-µCi dose of 212Pb-panitumumab (median survival >280 days). In summary, 212Pb-panitumumab is an excellent candidate for the treatment of HER1-positive disseminated i.p. disease. Furthermore, the potentiation of the therapeutic impact of 212Pb-pantiumumab by chemotherapeutics confirms and validates the importance of developing a multimodal therapy regimen.

The Next Generation of Dietitians: Implementing Dietetics Education and Practice in Integrative Medicine.

Integrative medicine is a quickly expanding field of health care that emphasizes nutrition as a key component. Dietitians and nutritionists have an opportunity to meet workforce demands by practicing dietetics and integrative medicine (DIM). The purpose of this article is to describe a DIM education program and practicum. We report the results of an interprofessional nutrition education and practicum program between the University of Kansas Medical Center (KUMC) Department of Dietetics and Nutrition and KU Integrative Medicine. This partnered program provides training that builds on the strong foundation of the Nutrition Care Process and adds graduate-level educational and practicum experiences in foundational integrative medicine knowledge, including nutritional approaches from a systems biology perspective, nutrigenomics, and biochemistry as the core knowledge to understand the root cause of a chronic disorder and to choose appropriate nutritional tools for interventions. This interprofessional KUMC program provides a dietetic internship, master's degree, and graduate certificate in DIM and fulfills a need for dietitians and nutritionists who seek careers practicing in an integrative medicine setting. The program fulfills expanding workforce needs to provide quality health care for patients with chronic illnesses.